What are the ongoing unmet needs in SR-GvHD, and how can ECP potentially address these?

The GvHD Hub was pleased to speak with Hildegard Greinix, Medical University of Vienna, Vienna, AT. We asked, What are the ongoing unmet needs in SR-GvHD, and how can ECP potentially address these? 

In this interview, Greinix discusses key unmet needs in the treatment of patients with steroid-refractory graft-versus-host disease (SR-GvHD), including variable and transient responses to available second-line therapies, treatment-related side effects, and the potential risk of infections or relapse. She explores the potential the role of extracorporeal photopheresis (ECP) in addressing these needs, highlighting its association with durable responses, favorable safety profile without generalized immunosuppression, and no reported interactions with other drugs. 

Key points 

• Corticosteroids remain the standard first-line treatment for GvHD; however, only up to 50–60% of patients respond, with many requiring subsequent salvage or second-line therapy.¹  
• Despite the availability of several treatment options for SR-GvHD, existing second-line agents may not adequately control GvHD activity and may be associated with several side effects, particularly profound systemic immunosuppression, an increased risk of infection, disease relapse, or unacceptable late effects.¹ 
• ECP is an immunomodulatory, leukapheresis-based procedure that has an established role in the management of SR-GvHD.^1,2  
• ECP promotes immune tolerance rather than causing generalized immunosuppression and has a favorable safety profile, with no reported drug interactions.^2,3 
• Sustained responses to ECP have been reported in patients with SR-GvHD.⁴ 
• Responses to systemic therapies for GvHD may vary by organ involvement.^5,6  
  • For example, in patients with chronic GvHD (cGvHD) in the ruxolitinib group of the REACH3 trial (NCT03112603), the Week 24 response rate was 8.6% in the lung, compared with 49.7% overall.⁵   
• ECP may help stabilize or improve pulmonary function in patients with pulmonary cGvHD, including bronchiolitis obliterans syndrome, although additional randomized controlled trials are needed to further define its clinical benefit in this setting.⁷ 
• Combination strategies involving ECP are increasingly being explored, with studies evaluating its use in combination with agents such as ruxolitinib and belumosudil.^8,9 
  • In a retrospective study, ruxolitinib in combination with ECP in patients with SR-acute GvHD (aGvHD) was associated with improved long-term control of aGvHD and a lower incidence of cGvHD at 1 year compared with ruxolitinib alone.⁹ 
• In summary, ECP may help address key unmet needs in SR-GvHD by providing durable disease control without generalized immunosuppression, while demonstrating a favorable safety profile and potential for use in different combination approaches.^1–4,8,9  

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